Deoxynivalenol induces caspase-8-mediated apoptosis through the mitochondrial pathway in hippocampal nerve cells of piglet

Abstract Background: Deoxynivalenol (DON) is a common trichothecene mycotoxin found throughout the world. DON has broad toxicity in animals and humans. Its neurotoxicity in vitro, however, is still unclear. This study was designed to investigate the hypothesis that DON toxicity in neurons occurs via the mitochondrial apoptotic pathway. Results: Using piglet hippocampal nerve cells (PHNCs), we evaluated the effects of varying concentrations of DON on typical indicators of apoptosis. The results obtained demonstrated that DON treatment inhibited PHNC proliferation and led to morphological, biochemical, and transcriptional changes consistent with apoptosis, including decreased mitochondrial membrane potential, mitochondrial release of CYCS and AIF, and increased abundance of active cleaved-caspase-9 and cleaved-caspase-3. Increasing concentrations of DON led to decreased Bcl-2 expression and increased expression of Bax and Bid, which in turn increased transcriptional activity of the transcription factors AIF and P53. Addition of a caspase-8 inhibitor abrogated these effects. Conclusion: These data reveal that DON induces apoptosis in PHNCs via the mitochondrial apoptosis pathway, and that caspase-8 plays an important role during apoptosis regulation.